WO2001047878A1 - Composes pyrrole/bases de mannich substitues destines a lutter contre la douleur et les reactions allergiques - Google Patents

Composes pyrrole/bases de mannich substitues destines a lutter contre la douleur et les reactions allergiques Download PDF

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Publication number
WO2001047878A1
WO2001047878A1 PCT/EP2000/012976 EP0012976W WO0147878A1 WO 2001047878 A1 WO2001047878 A1 WO 2001047878A1 EP 0012976 W EP0012976 W EP 0012976W WO 0147878 A1 WO0147878 A1 WO 0147878A1
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radical
aryl
phenyl
general formula
alkyl
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PCT/EP2000/012976
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German (de)
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WO2001047878A8 (fr
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Matthias Gerlach
Corinna Maul
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Grünenthal GmbH
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Priority to AU31611/01A priority Critical patent/AU782909B2/en
Priority to IL14981100A priority patent/IL149811A0/xx
Application filed by Grünenthal GmbH filed Critical Grünenthal GmbH
Priority to BR0016814-9A priority patent/BR0016814A/pt
Priority to MXPA02005793A priority patent/MXPA02005793A/es
Priority to KR1020027008185A priority patent/KR20020067571A/ko
Priority to NZ519975A priority patent/NZ519975A/en
Priority to SI200030262T priority patent/SI1246799T1/xx
Priority to PL00355413A priority patent/PL355413A1/xx
Priority to DE50004114T priority patent/DE50004114D1/de
Priority to US10/168,964 priority patent/US7034018B2/en
Priority to JP2001549351A priority patent/JP2003527350A/ja
Priority to EP00991220A priority patent/EP1246799B1/fr
Priority to AT00991220T priority patent/ATE252077T1/de
Priority to CA002396502A priority patent/CA2396502A1/fr
Priority to HU0203695A priority patent/HUP0203695A3/hu
Priority to SK730-2002A priority patent/SK286274B6/sk
Priority to DK00991220T priority patent/DK1246799T3/da
Publication of WO2001047878A1 publication Critical patent/WO2001047878A1/fr
Publication of WO2001047878A8 publication Critical patent/WO2001047878A8/fr
Priority to NO20023028A priority patent/NO20023028L/no
Priority to HK03102525A priority patent/HK1051855A1/xx
Priority to IL149811A priority patent/IL149811A/en

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    • C07D207/30—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
    • C07D207/32—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
    • C07D207/33—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms with substituted hydrocarbon radicals, directly attached to ring carbon atoms
    • C07D207/335—Radicals substituted by nitrogen atoms not forming part of a nitro radical
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    • C07D—HETEROCYCLIC COMPOUNDS
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    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
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    • C07D407/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00
    • C07D407/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings
    • C07D407/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond

Definitions

  • the invention relates to substituted pyrrole Mannich bases, processes for their preparation, medicaments containing these compounds and the use of these compounds for the production of medicaments.
  • Classic opioids such as the morphine
  • morphine are effective in the treatment of severe to very severe pain.
  • undesirable side effects include respiratory depression, vomiting, sedation, constipation and a development of tolerance.
  • the object of the present invention was therefore to provide new compounds which are particularly suitable as active ingredients in pharmaceuticals.
  • active ingredients are intended in particular for pain therapy and for the treatment of inflammatory and allergic reactions, drug and / or alcohol abuse, diarrhea, gastritis, ulcers, cardiovascular Diseases, urinary incontinence, depression, shock, migraines, narcolepsy, obesity, asthma, glaucoma, hyperkinetic syndrome, listlessness, bulimia, anorexia, catalepsy, for anxiolysis, for increasing vigilance and / or for increasing libido.
  • substituted pyrrole-Mannich bases of the general formula I below which have a pronounced analgesic effect, in particular also in the case of chronic pain, and which are also suitable for the treatment of inflammatory and allergic reactions, drug and / or
  • Alcohol abuse diarrhea, gastritis, ulcers, cardiovascular diseases, urinary incontinence, depression, shock, migraines, narcolepsy, obesity, asthma, glaucoma, hyperkinetic syndrome, listlessness, bulimia, anorexia, catalepsy, for anxiolysis, increased or vigilance enhancement and vigilance enhancement.
  • the invention therefore relates to substituted pyrrole Mannich bases of the general formula I,
  • R 2 CH (R 4 ) N (R 5 ) (R 6 ) means
  • R 4 an unsubstituted phenyl radical or at least one with Cu alkyl, C ⁇ . 3 -alkoxy, halogen, CF 3 -, CN-, O-phenyl or OH substituted phenyl radical, preferably an unsubstituted phenyl radical or one at least simply with methyl, tert-butyl, methoxy, F- , Cl-, Br- or CF 3 - substituted phenyl radical, particularly preferably an unsubstituted phenyl radical or a 2-methoxy-phenyl, 3-methoxy-phenyl, 4-methoxy-phenyl, 2-methyl phenyl, 3-methylphenyl, 4-methylphenyl, 2-tert-butylphenyl, 3-tert-butylphenyl, 4-tert-butylphenyl, 2-fluorophenyl , 3-fluorophenyl, 4-fluorophenyl, 2-chlorophenyl, 3-ch
  • R 7 H, COR 12 , a C 10 alkyl, an aryl, a heteroaryl, an aryl or heteroaryl radical bonded via a C 6 alkylene group, preferably a C 1. 6 alkyl or one via a C ⁇ . 2 -alkylene group means aryl radical,
  • R 8 H, a C 10 alkyl, an aryl, a heteroaryl or an aryl or heteroaryl radical bonded via a C 6 alkylene group, preferably a C 1.
  • 6 denotes alkyl or an aryl radical bonded via a C 1-4 alkylene group
  • R 9 H, COR 13 , a C ⁇ o-alky! -, an aryl, a heteroaryl or one via a C ⁇ . 6 -alkylene group bound aryl or heteroaryl radical, preferably a C ⁇ . 6 alkyl or one via a C ⁇ . 2 -alkylene group means aryl radical,
  • R 10 H, a C 10 alkyl, an aryl, a heteroaryl or an aryl or heteroaryl radical bonded via a C 6 alkylene group, preferably a C 6 alkyl or one over one C ⁇ . 2 -alkylene group bonded aryl radical means
  • R 11 H, a Ci.io-alkyl, an aryl, a heteroaryl or one over one
  • R 12 a C 10 alkyl, an aryl, a heteroaryl or an aryl or heteroaryl radical bonded via a C 6 alkylene group, preferably a C 6 alkyl or one via a C 1 2 -alkylene group means aryl radical,
  • R 13 a C 10 alkyl, an aryl, a heteroaryl or an aryl or heteroaryl radical bonded via a C 6 alkylene group, preferably a C 6 alkyl or one via a C 1 2 -alkylene group means aryl radical,
  • R 14 H, a C ⁇ _ ⁇ o-alkyl, an aryl, a heteroaryl or an aryl or heteroaryl radical bonded via a C ⁇ .6 alkylene group, preferably a C ⁇ - 6 alkyl or one via a C ⁇ 2 -alkylene group means aryl radical,
  • R 15 NHNH, NHR 14 , a C 1 -C 10 alkyl, an aryl, a heteroaryl or an aryl or heteroaryl radical bonded via a C 6 alkylene group, preferably a C 6 alkyl - Or means an aryl radical bonded via a C 2 alkylene group
  • Alkyl radicals are preferably understood to mean at least one hydrocarbon radical which is substituted at least once with halogen, OH, CN or CF 3 , particularly preferably with F, Cl, Br or OH. If these contain more than one substituent, these substituents can be the same or different.
  • the alkyl radicals can be branched, unbranched or cyclic.
  • alkyl radicals methyl, ethyl, propyl, 1-methylethyl, butyl, 1-methylpropyl, 2-methylpropyl, 1,1-dimethylpropyl, 1, 2-dimethylpropyl, 2,2-dimethylpropyl, hexyl, 1 : methylpentyl are particularly preferred , Heptyl, nonyl or decanyl.
  • An aryl radical is preferably at least one, with an OH, a halogen, preferably F, Br or Cl, a CF 3 , a CN, a C 6 alkyl, a C 1. 6 -alkoxy or a phenyl radical substituted phenyl or naphthyl radicals understood.
  • the unsubstituted or substituted phenyl radicals can also be fused with further rings.
  • a heteroaryl radical is understood to mean aromatic compounds which have at least one heteroatom, preferably nitrogen and / or oxygen and / or sulfur, particularly preferably nitrogen and / or oxygen and which preferably contain a halogen, a CF 3 -, a CN or an OH radical may be substituted.
  • the heteroaryl radical is particularly preferably a substituted or unsubstituted pyrrolyl, furfuryl, pyridine or thiophene radical.
  • the following substituted pyrrole Mannich bases are particularly preferred:
  • the invention further relates to processes for the preparation of substituted pyrrole-Mannich bases of the general formula I, which are characterized in that
  • R 4 has the meaning according to general formula I, in solution, preferably in an organic solvent, particularly preferably in toluene, in the presence of a base, preferably potassium carbonate or Boric anhydride, at a temperature of preferably -10 ° C to +110 ° C with secondary amines of the general formula III,
  • R 5 and R 6 have the meaning according to the general formula I, to amino compounds of the general formula IV
  • R 2 H and the radicals R 1 , R 3 , R 3 ' , R 3 " and R 7 to R 15 have the meaning according to the general formula I, to the pyrrole Mannich bases of the general formula I according to the invention, and the pyrrole-Mannich bases of the general formula I thus obtained are washed, preferably by washing with acetone, and isolated by the customary methods.
  • the substituted pyrrole-Mannich bases according to the invention are preferably synthesized on an automatic system from Zymark according to FIG. 1 and FIG. 2, as described below.
  • the compounds of general formula I can be combined with physiologically acceptable acids, preferably with hydrochloric acid, hydrobromic acid, sulfuric acid, methanesulfonic acid, formic acid, acetic acid, oxalic acid, succinic acid, tartaric acid, mandelic acid, fumaric acid, lactic acid, citric acid, glutamic acid and / or aspartic acid
  • Salt formation is preferably carried out in a solvent, particularly preferably in diethyl ether, diisopropyl ether, alkyl acetate, acetone and / or 2-butanone. Salt formation with trimethylchlorosilane in methyl ethyl ketone is very particularly preferred.
  • Formula I are toxicologically harmless and therefore represent suitable active pharmaceutical ingredients.
  • the invention therefore furthermore also relates to medicaments which contain at least one substituted pyrrole Mannich base of the general formula I and optionally further active ingredients and / or auxiliaries as the active ingredient.
  • the medicament can preferably also contain a mixture of enantiomers of at least one substituted pyrrole-Mannich base of the general formula I as the active ingredient, the mixture preferably not having the enantiomers in equimolar amounts.
  • the relative proportion of one of the enantiomers is particularly preferably 5 to 45 mol%, very particularly preferably 10 to 40 mol%, based on the mixture of the enantiomers.
  • the medicaments are preferably used to treat / combat pain, in particular chronic pain, and / or inflammatory reactions and / or allergic reactions and / or substance abuse and / or alcohol abuse and / or diarrhea and / or gastritis and / or ulcers and / or cardiovascular diseases and / or urinary incontinence and / or depression and / or shock states and / or migraines and / or narcolepsy and / or overweight and / or asthma and / or glaucoma and / or hyperkinetic syndrome and / or
  • carrier materials In addition to at least one substituted pyrrole-Mannich base of the general formula I, carrier materials, fillers, solvents, diluents, dyes and / or binders are used to prepare corresponding pharmaceutical formulations.
  • the choice of excipients depends on whether the drug is to be administered orally, intravenously, intraperitoneally, intradermally, intramuscularly, intranasally, buccally or locally, for example for infections of the skin, mucous membranes and eyes.
  • the preparations in the form of tablets, dragees, capsules, granules, drops, juices and syrups are suitable for oral administration, and solutions, suspensions, easily reconstitutable dry preparations and sprays are suitable for parenteral, topical and inhalative administration.
  • pyrrole-Mannich bases of the general formula I according to the invention in a depot in dissolved form or in a plaster, optionally with the addition of agents which promote skin penetration, are suitable percutaneous application preparations. From oral or percutaneous
  • Formulations, the compounds of general formula I according to the invention can be released with a delay.
  • the amount of active ingredient to be administered to the patient varies depending on the weight of the patient, the type of application, the indication and the severity of the disease.
  • the action of the pyrrole Mannich bases according to the invention is determined in particular by the affinity for the N-methyl-D-aspartate (NMDA) receptor family, for ⁇ -adrenergic receptors and opioid receptors.
  • NMDA N-methyl-D-aspartate
  • the animals were placed individually in observation cages.
  • a capper station for closing the reaction tubes
  • a robot 1 for closing the reaction tubes
  • a robot 1 for closing the reaction tubes
  • a robot 2 for closing the reaction tubes
  • the robot 1 moving the reaction tubes and the robot 2 moving the reagents in the reaction tubes are pipetted
  • a temperature-controlled reactor block section 4
  • stirring blocks section 5
  • a filtration station section 6 in which the reaction solution is filtered off.
  • FIG. 2 also includes a robot 1 (item 1) and a robot 2 (item 2), both robots bringing the vessels with the reaction products to the various stations on which the synthesis products from the automatic synthesis system according to FIG. 1 are processed.
  • the synthesis products are mixed with acetone on a vortexer (Section 3), mixed in a spin reactor (Section 4) and the acetone is then decanted off.
  • a round-bottom tube made of glass (diameter 16 mm, length 125 mm) with a thread was provided manually with a stirrer and closed on the capper station (item 1) according to FIG. 1 with a screw cap with a septum.
  • Robot 1 (Section 2) placed the tube in the reactor block heated to 0 ° C.
  • Robot 2 (item 3) added the following reagents in succession: 1.) 1 ml of a 0.1 M solution of pyrrole or a substituted pyrrole compound of the general formula VI in acetonitrile
  • the iminium salts were previously prepared as indicated in the examples below.
  • the reaction mixture was then stirred at 18 ° C. in one of the stirring blocks (item 5) for 960 minutes.
  • the reaction solution was then filtered off at the filtration station (Section 6).
  • the solvent was first removed in a vacuum centrifuge.
  • the rack with the tubes was then placed manually on a vortexer (item 3) according to FIG. 2.
  • the reaction mixture was mixed with 2 ml of acetone.
  • the spin reactor (Section 4), the mixture was mixed thoroughly for 10 minutes and finally the acetone was decanted off. This process was carried out three more times and finally the solvent was removed in a vacuum centrifuge.
  • stage 1- (2-methoxy-benzylidene) pyrrolidinium chloride
  • the preparation was carried out according to general synthesis instructions 4 from 1-ethyl-1 H-pyrrole and (2-methoxy-benzylidene) dimethyl ammonium chloride.
  • the preparation was carried out in accordance with general synthesis instructions 4 from 1-phenyl-1-H-pyrrole and benzylidene-dimethyl-ammonium chloride.
  • the preparation was carried out according to general synthesis instructions 4 from 2-pyrrol-1-yl-phenylamine and 1- (2-methyl-benzylidene) pyrrolidinium chloride.
  • the preparation was carried out according to general synthesis instructions 4 from 2-pyrrol-1-yl-thiobenzamide and dimethyl- (2-methyl-benzylidene) ammonium chloride.
  • Phenyl-1 H-pyrrole and 1- (4-bromo-benzylidene) pyrrolidinium chloride which according to
  • Example 4 has been prepared from 4-bromobenzaldehyde and pyrrolidine.
  • Example 24 has been prepared from 4-bromobenzaldehyde and pyrrolidine.
  • the preparation was carried out according to general synthesis instructions 4 from 4-pyrrol-1-yl-methyl-pyridine and 1- (4-bromo-2-fluorobenzylidene) pyrrolidinium chloride, which according to Example 4 from 4-bromo-2-fluorobenzaldehyde and Pyrrolidine has been produced.
  • Methyl-1 H-pyrrole and 1- (4-trifluoromethyl-benzylidene) -piperidinium chloride which was prepared according to Example 3 from 4-trifluoromethylbenzaldehyde and piperidine.
  • Example 36 2- ⁇ 2 - [(3-bromo-4-fluorophenyl) pyrrolidin-1-ylmethyl] pyrrol-1-ylmethyl ⁇ pyridine
  • the preparation was carried out according to general synthesis instructions 4 from 4-pyrrol-1-yl-methyl-pyridine and 1- (3-bromo-4-fluorobenzylidene) pyrrolidinium chloride, which according to Example 4 from 3-bromo-4-fluorobenzaldehyde and Pyrrolidine has been produced.
  • the investigated compounds according to the invention showed an inhibition of serotonin reuptake.
  • the investigated compounds according to the invention showed an analgesic effect.

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  • Pyrrole Compounds (AREA)

Abstract

Composés pyrrole/bases de Mannich substitués de formule générale (I) dans laquelle R1 représente H, un reste alkyle C¿1-10?, aryle, hétéroaryle ou un reste aryle, hétéroaryle, CN, Br, Cl ou OH lié par l'intermédiaire d'un groupe alkylène C1-6, R?2¿ représente CH(R?4)N(R5)(R6), R3, R3', R3''¿ représentent, tous ou indépendamment les uns des autres, H, F, Cl, Br, CF¿3?, CN, NO2, SO2NH2, NHR?7, SR8, OR9, CO(OR10), CH¿2CO(OR?11), COR15¿, un reste alkyle C¿1-10?, un reste aryle, un reste hétéroaryle ou un reste aryle ou hétéroaryle lié par l'intermédiaire d'un groupe alkylène C1-6, R?4¿ représente un reste phényle non substitué ou un reste phényle substitué au moins de manière simple par alkyle C¿1-4?, alcoxy C1-3, halogène, CF3, CN, O-phényle ou OH. La présente invention concerne également un procédé de préparation desdits composés, des médicaments les contenant, ainsi que l'utilisation de ces composés pour fabriquer des médicaments. Ces principes actifs sont particulièrement adaptés à la thérapie de lutte contre la douleur et au traitement de réactions inflammatoires et allergiques, de la toxicomanie et/ou de l'alcoolisme, de la diarrhée, de la gastrite, des ulcères, des maladies cardio-vasculaires, de l'incontinence urinaire, de la dépression, des états de choc, des migraines, de la narcolepsie, de la surcharge pondérale, de l'asthme, du glaucome, du syndrome hyperkynétique, de l'athymie, de la boulimie, de l'anorexie, et de la catalepsie, ainsi que pour provoquer l'anxiolyse, augmenter la vigilance et/ou la libido.
PCT/EP2000/012976 1999-12-27 2000-12-20 Composes pyrrole/bases de mannich substitues destines a lutter contre la douleur et les reactions allergiques WO2001047878A1 (fr)

Priority Applications (20)

Application Number Priority Date Filing Date Title
SK730-2002A SK286274B6 (sk) 1999-12-27 2000-12-20 Substituované Mannichove bázy pyrolov na použitiena potláčanie bolesti a alergických reakcií, spôsob ich prípravy, liek a použitie
US10/168,964 US7034018B2 (en) 1999-12-27 2000-12-20 Substituted pyrrole mannich bases to combat pain and allergic reactions
BR0016814-9A BR0016814A (pt) 1999-12-27 2000-12-20 Bases de mannich de pirrol substituìdas
MXPA02005793A MXPA02005793A (es) 1999-12-27 2000-12-20 Bases de mannich sustituidas con pirrol para combatir el dolor y reacciones alergicas.
KR1020027008185A KR20020067571A (ko) 1999-12-27 2000-12-20 통증 및 알레르기성 반응에 대응하기 위한 치환된 피롤만니히 염기
NZ519975A NZ519975A (en) 1999-12-27 2000-12-20 Substituted pyrrole mannich bases to combat pain and allergic reactions
SI200030262T SI1246799T1 (en) 1999-12-27 2000-12-20 Substituted pyrrole mannich bases to combat pain and allergic reactions
PL00355413A PL355413A1 (en) 1999-12-27 2000-12-20 Substituted pyrrole mannich bases to combat pain and allergic reactions
EP00991220A EP1246799B1 (fr) 1999-12-27 2000-12-20 Composes pyrrole/bases de mannich substitues destines a lutter contre la douleur et les reactions allergiques
AU31611/01A AU782909B2 (en) 1999-12-27 2000-12-20 Substituted pyrrole mannich bases to combat pain and allergic reactions
JP2001549351A JP2003527350A (ja) 1999-12-27 2000-12-20 置換ピロールマンニッヒ塩基
DE50004114T DE50004114D1 (de) 1999-12-27 2000-12-20 Substituierte pyrrol-mannichbasen zur bekämpfung von schmerzen und allergischen reaktionen
AT00991220T ATE252077T1 (de) 1999-12-27 2000-12-20 Substituierte pyrrol-mannichbasen zur bekämpfung von schmerzen und allergischen reaktionen
CA002396502A CA2396502A1 (fr) 1999-12-27 2000-12-20 Bases de mannich pyrrole substitues
HU0203695A HUP0203695A3 (en) 1999-12-27 2000-12-20 Substituted pyrrole mannich bases preparation and use thereof, and pharmaceutical composition containing the same
IL14981100A IL149811A0 (en) 1999-12-27 2000-12-20 Substituted pyrrole mannich bases to combat pain and allergic reactions
DK00991220T DK1246799T3 (da) 1999-12-27 2000-12-20 Substituerede pyrrol-Mannich-baser til bekæmpelse af smerter og allergiske reaktioner
NO20023028A NO20023028L (no) 1999-12-27 2002-06-21 Substituerte pyrrol-mannich baser for bekjemping av smerter og allergiske reaksjoner
HK03102525A HK1051855A1 (en) 1999-12-27 2003-04-09 Substituted pyrrole mannich bases to combat pain and allergic reactions
IL149811A IL149811A (en) 1999-12-27 2004-01-01 Pirols are transformed as manic bases for the treatment of pain and allergic reactions

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE19963174.3 1999-12-27
DE19963174A DE19963174A1 (de) 1999-12-27 1999-12-27 Substituierte Pyrrol-Mannichbasen

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WO2001047878A1 true WO2001047878A1 (fr) 2001-07-05
WO2001047878A8 WO2001047878A8 (fr) 2001-10-04

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PCT/EP2000/012976 WO2001047878A1 (fr) 1999-12-27 2000-12-20 Composes pyrrole/bases de mannich substitues destines a lutter contre la douleur et les reactions allergiques

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EP (1) EP1246799B1 (fr)
JP (1) JP2003527350A (fr)
KR (1) KR20020067571A (fr)
CN (1) CN1247542C (fr)
AR (1) AR027058A1 (fr)
AT (1) ATE252077T1 (fr)
AU (1) AU782909B2 (fr)
BR (1) BR0016814A (fr)
CA (1) CA2396502A1 (fr)
CO (1) CO5261489A1 (fr)
CZ (1) CZ20022239A3 (fr)
DE (2) DE19963174A1 (fr)
DK (1) DK1246799T3 (fr)
ES (1) ES2208466T3 (fr)
HK (1) HK1051855A1 (fr)
HU (1) HUP0203695A3 (fr)
IL (2) IL149811A0 (fr)
MX (1) MXPA02005793A (fr)
NO (1) NO20023028L (fr)
NZ (1) NZ519975A (fr)
PE (1) PE20010988A1 (fr)
PL (1) PL355413A1 (fr)
PT (1) PT1246799E (fr)
RU (1) RU2002120468A (fr)
SK (1) SK286274B6 (fr)
TR (1) TR200302178T4 (fr)
WO (1) WO2001047878A1 (fr)
ZA (1) ZA200204199B (fr)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE10261130A1 (de) * 2002-12-20 2004-07-01 Grünenthal GmbH Arzneimittel enthaltend substituierte 2,5-Diaminomethyl-1H-pyrrole
WO2015030514A1 (fr) * 2013-08-29 2015-03-05 주식회사 대웅제약 Dérivé de tétrahydrocyclopentapyrrole et son procédé de préparation

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GB0016453D0 (en) * 2000-07-04 2000-08-23 Hoffmann La Roche Pyrrole derivatives
PT1471054E (pt) * 2002-01-11 2009-09-23 Daiichi Sankyo Co Ltd Derivado de aminoálcool ou derivado de ácido fosfónico e composição medicinal que os contém
CN101099041A (zh) * 2004-11-09 2008-01-02 亨卓克·康尼里尔斯·范哈尔斯丽尔 空气动力风扇发电系统
CN102221678A (zh) * 2011-05-17 2011-10-19 重庆长安汽车股份有限公司 一种电池系统在线寿命计算方法
TW201416348A (zh) * 2012-08-29 2014-05-01 Gruenenthal Chemie 以氟甲基取代之吡咯甲醯胺

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EP0038536A1 (fr) * 1980-04-18 1981-10-28 E.I. Du Pont De Nemours And Company 4,5-Diaryl-alpha-(polyfluoroalkyl)-1H-pyrrole-2-méthanamines anti-inflammatoires
US5935990A (en) * 1996-12-10 1999-08-10 G.D. Searle & Co. Substituted pyrrolyl compounds for the treatment of inflammation

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Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE10261130A1 (de) * 2002-12-20 2004-07-01 Grünenthal GmbH Arzneimittel enthaltend substituierte 2,5-Diaminomethyl-1H-pyrrole
US7776903B2 (en) 2002-12-20 2010-08-17 Gruenenthal Gmbh Pharmaceutical preparations containing substituted 2,5-diaminomethyl-1H-pyrroles
WO2015030514A1 (fr) * 2013-08-29 2015-03-05 주식회사 대웅제약 Dérivé de tétrahydrocyclopentapyrrole et son procédé de préparation
US10039747B2 (en) 2013-08-29 2018-08-07 Daewoong Pharmaceutical Co., Ltd. Tetrahydrocyclopentapyrrole derivatives and a method for preparing the same

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EP1246799A1 (fr) 2002-10-09
EP1246799B1 (fr) 2003-10-15
CA2396502A1 (fr) 2001-07-05
DE50004114D1 (de) 2003-11-20
HUP0203695A3 (en) 2004-12-28
MXPA02005793A (es) 2004-08-12
WO2001047878A8 (fr) 2001-10-04
DE19963174A1 (de) 2001-07-12
HUP0203695A2 (hu) 2003-04-28
KR20020067571A (ko) 2002-08-22
ZA200204199B (en) 2004-02-10
CZ20022239A3 (cs) 2003-04-16
ATE252077T1 (de) 2003-11-15
CN1414950A (zh) 2003-04-30
CO5261489A1 (es) 2003-03-31
TR200302178T4 (tr) 2004-01-21
DK1246799T3 (da) 2004-02-16
HK1051855A1 (en) 2003-08-22
US20030023100A1 (en) 2003-01-30
SK7302002A3 (en) 2002-11-06
AU3161101A (en) 2001-07-09
AR027058A1 (es) 2003-03-12
NZ519975A (en) 2004-02-27
PL355413A1 (en) 2004-04-19
ES2208466T3 (es) 2004-06-16
PT1246799E (pt) 2004-03-31
PE20010988A1 (es) 2001-10-06
IL149811A0 (en) 2002-11-10
JP2003527350A (ja) 2003-09-16
NO20023028D0 (no) 2002-06-21
CN1247542C (zh) 2006-03-29
IL149811A (en) 2006-07-05
RU2002120468A (ru) 2004-01-10
SK286274B6 (sk) 2008-06-06
US7034018B2 (en) 2006-04-25
AU782909B2 (en) 2005-09-08
BR0016814A (pt) 2002-09-10
NO20023028L (no) 2002-08-20

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